| Many diseases in neurological department complicate with psychiatric syndromes. Organic mental disorders in the brain are a kind of disorder caused by the alteration of the form in the brain. Among them post stroke depression is the most common one. Post stroke depression is a more common complication of stroke. People with stroke are often of old age, so choosing a more suitable drug is more important in the treatment of post stroke depression. Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by the gradual impairment of memory function and accumulation of neurofibrillary tangles and neuritic plaques in brain regions subserving cognitive functions. The amyloid β, the major component of neuritic plaques, is an amino-acid proteolytic fragment of the amyloid precursor protein. Incubation of Aβ in vitro results in a concentration- and time-dependent formation of neurotoxic fibrils, similar to those characteristic of amyloid-containing plaques present in the brains of AD patients. Our experiment is to explore the neuroprotective effect of antipsychiatric drugs on Aβ (Aβ25-35) induced cell apoptosis. A large quantity of antipsychiatric drugs have come out recently. Atypical antipsychotic drugs are widely used in the treatment of schizophrenia and antidepressant venlafaxine is widely used in the treatment of depression, especially post stroke depression. And clinical evidence has shown that early and prolonged intervention with these drugs will improve the long-term outcome. It is still unclear, however whether these drugs are also neuroprotective. Some studies have demonstrated that the atypical antipsychotic drugs clozapine, olanzapine and quetiapine can protect PC12 cells from death induced by hydrogen peroxide, β-amyloid peptide and MPP+. To clarify this matter , we used PC12 cells cultures,the LDH and the MTT assays to determine whether various concentrations of these drugs are protective. The present study examined the protective effects of the atypical antipsychotic drugs olanzapine,quetiapine and the antidepressant venlafaxine on PC 12 cells after serum withdrawal and those of the antidepressant venlafaxine on injury of PC12 cells induced by β-amyloid 25-35. This study also explored the mechanisms underlying these effects. To explore venlafaxine's protective mechanism, Western blot was used to examine the protein expression of Bcl-2 and histoimmunology was used to test the protein expression of Bax.The results demonstrated that (1) The most pronounced changes were observed at concentrations of 100μM olanzapine,50μM quetiapine,20μM venlafaxine (p<0.01), and these changes were significantly different from their respective control groups. Among them 20μM venlafaxine has the greatest change. At twice the concentration of each drug (200μM olanzapine,100μM quetiapine,40μM venlafaxine), there was no protection against pc12 cell death induced by serum withdrawal. Based on the most effective protective concentration of each drug (100μM olanzapine,50μM quetiapine,20μM venlafaxine), a time course study was done, and results are shown in Fig.5. Under serum free-conditions, pc12 cell viability was reduced in a time-dependent manner. Olanzapine,quetiapine and venlafaxine significantly protected pc 12 cells within 48 hours in comparison with the serum-free control group (p<0.01). (2)western blot analysis of Bcl-2 in PC12 cells indicates that β-amyloid 25-35 decreased the level of Bcl-2, but this decrease can be attenuated by treatment with 20μM venlafaxine. This finding suggest that venlafaxine may exert a neuroprotective function through the modulation of the level of Bcl-2. Levels of Bax are not significantly different in each group. In summary, we have used in vitro cell culture to determine cell protection of several psychotic drugs after serum withdrawal and Aβ25-35-induced cell apoptosis. The mechanism of venlafaxine's protective effect on Aβ25-35-induced cell apoptosis may be relevant to the increase of Bcl-2. In this way, this...
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